19.11.2021 - A deep-dive into SGLT1
SGLT1 - Sodium/Glucose Cotransporter 1 - SLC5A1
Targets and Family: SGLT1 belongs to the Solute:Sodium Symporter Family (SSSF, TCDB: 2.A.21). Since it is a human transporter, it’s also classified as an SLC transporter: SGLT1 equals to SLC5a1 and belongs to the sodium/glucose cotransport family (SLC5).
Function: Absorption of D-glucose in the small intestine using the sodium transmembrane gradient, which is established by the Na+/K+ ATPase. Na+/sugar symport occurs with 2:1 stoichiometry. SGLT1 is known as a high-affinity / low-capacity transporter, having an affinity for its main substrate D-glucose of 0.5 mM and a transport rate of 20 molecules per second.
Organism and Localisation: SGLT1 is a mammalian transporter, localized within the plasma membrane of the small intestine, specifically in the lower segments. Here the high affinity allows for absorption of D-glucose, which was not absorbed by SGLT2. Defects in SGLT1 function can lead to congenital glucose/galactose malabsorption (GGM), an autosomal recessive disorder.
Substrates and Inhibitors: D-glucose is the physiological most relevant substrate. Methyl-D-glucose is often used for experiments on SGLT1, due to the fact that it is not metabolized, but exhibits similar transport properties as D-glucose. Other substrates are galactose; some transport activity was also observed for D-xylose, 2-Desoxy-D-glucose and 3-O-Methyl-D-glucose. Sugar transport is coupled to Na+ translocation, but Na+ can be replaced by Li+ and H+. Well-characterized inhibitors are Phlorizin, which has a very high affinity in the nM range for the extracellular site of SGLT1, but very week affinity for the intracellular site. SGLT1 is also inhibited by Phloretin with an IC50 of ~ 100 µM.
Related Transporters: SGLT2 has a different tissue distribution than SGLT1, and is expressed predominantly in the upper segments of the small intestine. It has a higher transport capacity, but lower affinity for D-glucose and a 1:1 Na+/D-glucose transport stoichiometry. Other functionally related transporters belong to the GLUT family, which are human D-glucose uniporters or the SWEET family, which contain sugar transporters first found in plants. Highly relevant is also the prototypical and famous bacterial proton-coupled lactose transporter LacY from E.coli.
Read this publication - SSM-based electrophysiology, a label-free real-time method reveals sugar binding & transport events in SGLT1
Learn more from this Poster about a novel approach to detect electrogenic transporter activity in intact cells applied to investigate iPSC derived cardiomyocytes and neurons
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Data and Applications